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Nutraceutical modulation of lipotoxicity and the development of a tool to monitor palmitate induced sub-cellular dysfunction. - by Dean Frederick Ashley. Over 64.3% of the UK are currently overweight or obese according to the NHS survey, a number that has continued to increase throughout the beginning of the 21st century. Inherently this increases the use of NHS resources through an increased prevalence of obesity associated diseases, including type 2 diabetes. To address this, changes to individual’s diets are required and a greater understanding of the sub-cellular mechanisms, that lead to insulin resistance and type 2 diabetes, need to be further understood. In this thesis, C2C12 myotubes & S. cerevisiae are treated with tunicamycin or the saturated fatty acid palmitate (Chapter 3), to create models of ER stress and lipotoxicity, respectively. These models are then used in subsequent chapters to study the nutraceutical modulation (Chapters 4 & 5) and sub-cellular aberrations of lipotoxicity (Chapter 6). Palmitate, the most prevalent saturated fatty acid elevated during obesity, was exposed to C2C12 myotubes in combination with the artificial sweetener Acesulfame-K (Ace-K)(Chapter 4) and the polyphenol compound curcumin (Chapter 5). Previous studies have highlighted a need for a more comprehensive understanding surrounding the possible effects of Ace-K. Using rtPCR and mass spectrometry, this thesis shows Ace-K can exacerbate palmitate induced inflammation, lipid intermediate accumulation and insulin resistance, through an AMPK dependant mechanism. Further consolidating the need for more in depth in vivo studies to understand the compound’s risks. The same techniques are then used to study the effects of curcumin, in combination with palmitate, on C2C12 mouse skeletal muscle cells. Previous studies have shown curcumin alleviates palmitate induced inflammation, general lipid accumulation and insulin resistance. However, the specific lipid intermediate responsible for these changes remained unknown. This study demonstrates curcumin decreases diacylglycerol accumulation, through a βoxidative dependant mechanism, whilst simultaneously increasing long chain ceramide concentrations, through PERK signalling. This provides a possible combining mechanism for curcumins anti-inflammatory and cytotoxicity phenotypes. Lastly (Chapter 6), a protocol for monitoring the sub-cellular relocalisation of proteins and lipids is developed using the Localisation of organelle proteins by isotopic tagging (LOPIT) technique. Organelles are separated based on their densities and proteomic and lipidomic LCMS open-profiling is used to quantify proteins and lipids abundances across the differential centrifugation fractions. Known organelle marker proteins are then used by the Bayesian ANalysis of Differential Localisation Experiments (BANDLE) algorithm to assign organelle localisations to proteins and lipids with previously unknown organelle localisations, whilst simultaneously identifying species that have changed location following palmitate treatment. This offers a combined workflow to study the sub-cellular relocalisation of proteins and lipids that can be applied to a range of perturbations within C2C12 mouse skeletal muscle cells., BBSRC iCASE studentship

Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests.

BACKGROUND The profitability of farming varies based on factors such as a crop's market value, input costs and occurrence of resistant pests, all capable of altering the value of pest management tactics in an integrated pest management program. We provide a framework for calculating expected yield and expected net revenue of pest management scenarios, using the soybean aphid (Aphis glycines) as a case study. Foliar insecticide and host‐plant resistance are effective management tactics for preventing yield loss from soybean aphid outbreaks; however, pyrethroid‐resistant aphid populations pose a management challenge for farmers. We evaluated eight scenarios relevant to soybean aphid management in Iowa with varying probabilities of aphid outbreaks and insecticide‐resistant aphids occurring. RESULTS Our equation suggests that insecticide use is profitable when the probability of an aphid outbreak is ≥29%, and soybean production will become more costly with increasing probability of pyrethroid‐resistant aphids. If farmers continue to use pyrethroids, they will not experience financial consequences from pyrethroid‐resistant aphids until the chance of insecticide resistance is 48%. Aphid‐resistant varieties provided consistent yield and offered the highest net revenue under all conditions. CONCLUSION This framework can be used for other crop–pest systems to evaluate the profitability of management tactics and investigate how resistance impacts revenue for farmers. Including the cost of resistance in crop budgets can help farmers and agronomic consultants comprehend these impacts and enhance decision‐making to increase revenue and curb resistance development., We developed a framework to evaluate the profitability of management scenarios across varying probabilities of a pest outbreak occurring and probabilities that the pest is resistant to the management tactic.

Farmers face many choices when selecting seed for soybean (Glycine max (L.) Merr.) production, including highly desired herbicide tolerance traits. Despite the convenience of herbicide tolerance, resistant weeds and technology fees may reduce utility and profitability of these varieties, especially when commodity prices are low. Sporadic outbreaks of soybean aphid (Aphis glycines Matsumura, Hemiptera: Aphididae) that require insecticide use for optimal yield can be a further complication for farmers in Iowa. Soybean aphid-resistant varieties are commercially available, but in limited genetic backgrounds without herbicide tolerance. We hypothesized yield and value of resistance traits will vary based on the environment. We established plots at two locations with different risks of soybean aphid outbreaks and used two planting dates at each location to mimic different yield environments. In 2016 and 2017, we planted four varieties that varied in their susceptibility to soybean aphids and glyphosate, and applied insecticides if aphid populations reached an economic threshold. Regardless of genetic background, aphid-resistant varieties prevented populations from reaching the economic threshold at all environments. We observed no significant difference in yield between resistant and susceptible varieties, revealing this trait is as effective at protecting yield as an insecticide application on susceptible varieties at the high-risk location. We also explored the value of each variety in different environments. Resistant varieties produced greater potential net revenue than susceptible varieties at the high-risk location, while the opposite occurred at the low-risk location. Resistant varieties with herbicide tolerance, if made available, would be the most valuable across all environments.

Chemical defoliation of seed corn production fields accelerates seed maturation and desiccation and expedites seed harvest. Early seed harvest is important to minimize the risk of frost damage while in the field. This newly adopted seed production practice also allows seed companies to plan harvest and manage dryer space more efficiently. However, premature defoliation may interfere with the migration of oil bodies within embryo cells during desiccation and affect seed germination and vigor. The objective of this study was to investigate the effect of chemical defoliation on the migration patterns of oil bodies within embryo cells during desiccation. Chemically defoliated and non-defoliated plants from five commercial hybrid seed corn fields were sampled in 2014 and 2015. Whole ears with husks were harvested before and after defoliant application at 600 g H2O kg−1 fresh weight (fw), and weekly thereafter until seed reached approximately 300–350 g H2O kg−1 fw. Ten embryos extracted from center-row seeds were fixed to stop metabolic processes, then sliced, processed, and photographed using scanning transmission electron microscopy. The oil bodies within embryo cells followed normal migration patterns according to seed moisture content, regardless of defoliation treatment. Seed germination and vigor were verified and were not significantly affected by defoliation. Chemical defoliation is a viable production practice to accelerate seed corn desiccation and to manage harvest and seed dryer availability more efficiently without negatively affecting seed germination and vigor.

Corn, Zea mays L. (Cyperales: Poaceae), production is essential to Iowa’s economy and provides food, feed, and fuel beyond the state. Farmers face a number of challenges in corn production, including insect pests, and understanding farmers’ perceptions and concerns is critical for extension personnel to provide adequate and relevant programming. The Iowa State University Agriculture and Natural Resources Crops Team conducted a survey of Iowa farmers and agribusiness professionals during the 2019–2020 extension season. The goal was to understand farmer perceptions of corn pests and whether farmers experienced challenges with resistance to Bt traits or insecticides. Additionally, we aimed to realize farmers’ confidence in developing resistance management plans and discussing those needs with their input suppliers and advisors. Our survey revealed that northern corn rootworm, Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae), was the pest of greatest concern across the state. People were generally more concerned about belowground Bt trait performance than aboveground traits, though only 12% of respondents reported Bt trait failure for corn rootworms. In general, people were not concerned about the performance of seed treatments or soil- or foliar-applied insecticides. Farmers generally felt very confident in developing a resistance management plan and discussing their needs with their advisors. The results of this survey will be used to target extension programming throughout the state and increase confidence for farmers and agribusiness employees to discuss resistance management plans together.

Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), continues to be an economically important insect pest of soybean in the northcentral region of the United States since its first report in 2000. Control has traditionally relied on foliar applications of pyrethroid and organophosphate insecticides; however, recent confirmed failures of pyrethroids in the region have prompted immediate management concerns. Insecticidal modes of action are limited, and there is a need for assessing residual efficacy of exisiting and new insecticides for soybean aphid. We developed a field-based protocol to evaluate the residual efficacy of treated foliage, and tested our method with two insecticides. Our residual testing protocol can be utilized for residual efficacy evaluations of other pests and in other systems.

Purpose Management guidelines for infants with chylothorax lack substantial evidence. We sought to identify variables that impact outcomes in these patients in order to develop an evidence-based management algorithm. Methods We retrospectively reviewed the medical records of all infants diagnosed with chylothorax from June 2005 to December 2014 at our institution. Data collected included demographics, chest tube output (CTO), medical and dietary interventions, surgical procedures, and absolute lymphocyte count (ALC). Outcomes analyzed included death, sepsis, necrotizing enterocolitis (NEC), requiring surgery, and success of therapy, defined as CTO decrease by >50% within 7days. Results Of 178 neonates with chylothorax, initial therapy was high medium chain triglyceride (MCT) feedings in 106 patients, nothing by mouth (NPO), total parenteral nutrition (TPN) in 21, and NPO/TPN plus octreotide in 45. Octreotide use in addition to NPO/TPN revealed no significant differences in any outcome including success (47% vs. 43%, p =0.77). Initial CTO and ALC correlated with needing surgery ( p =0.002 and p =0.006, respectively), and with death ( p =0.028 and p =0.043, respectively). ALC also correlated with sepsis ( p Conclusions Octreotide has no advantage over NPO/TPN alone in infants with chylothorax. CTO and ALC predict requiring surgery. We propose a management guideline based on CTO and ALC without a role for octreotide. Type of study Retrospective case–control study. Level of evidence 3

Purpose: Mixed efficacy results of autologous skeletal muscle precursor cell therapy in women with chronic intrinsic urinary sphincter deficiency have increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 (C-X-C motif chemokine 12) and skeletal muscle precursor cells on chronic urinary sphincter regeneration in chronic intrinsic urinary sphincter deficiency.Materials and Methods: Five million autologous skeletal muscle precursor cells or 100 ng CXCL12 were injected in the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6-month history) intrinsic urinary sphincter deficiency. These treatment groups of 3 monkeys per group were compared to a group of 3 with no intrinsic urinary sphincter deficiency and no injection, and a group of 3 with intrinsic urinary sphincter deficiency plus vehicle injection. Maximal urethral pressure was measured at rest, during stimu...

We summarize the current state of knowledge regarding cell therapy for stress urinary incontinence and introduce new approaches of using regenerative pharmacology as an adjunct or replacement for cell therapy.We reviewed the literature by searching PubMed®, Ovid and Biological Abstracts. The period searched was 1975 to December 2015. The inclusion terms separately or in combination were stress urinary incontinence, cell therapy, chemokine, vascularization, innervation, secretome and/or animal models. Epublished articles were not included. We did not exclude articles based on impact factor.Cell therapy is currently proposed to restore functional muscle cells and aid in closure of the sphincter in women with sphincter associated incontinence. Clinical trials have included small numbers of patients and results have varied depending on the patient cohorts and the cells used. Results of preclinical studies have also varied but show a more favorable outcome. This difference was most likely explained by the fact that animal modeling is not directly translatable to the human condition. However, preclinical studies have identified an exciting new approach to regeneration of the urinary sphincter using the components of cells (secretomes) or chemokines that home reparative cells to sites of injury.Cell therapy will continue to be explored. However, a regenerative pharmacological approach to the treatment of stress urinary incontinence holds the promise of bypassing the lengthy and expensive process of cell isolation and also increasing the availability of treatment in many clinical settings. This approach requires careful preclinical modeling and attention to its health benefit-to-risk ratio.

Objective Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12. Methods Ten adult male cynomolgus monkeys were used. Two were used for study of normal male nonhuman primate genitourinary anatomy. Five were used for measures of sexual behavior, peak intra-corporal pressure (ICP), abdominal leak point pressures (ALPP) 3 and 6-months post open radical prostatectomy (ORP). Three additional ORP animals received ultrasound-guided peri-urethral injection of chemokine CXCL12 6 weeks after ORP, and UI/ED evaluated for up to 3 months. Results The anatomy, innervation, and vascular supply to the prostate and surrounding tissues of these male NHPs are substantially similar to those of human beings. ORP resulted in complete removal of the prostate gland along with both neurovascular bundles and seminal vesicles while permitting stable restoration of vesico-urethral patency. ORP produced sustained (6 months) decreases in ALPP, ICP's, and sexual function. Transurethral injection of chemokine CXCL12 was feasible and had beneficial effects on erectile and urinary function. Conclusions ORP in NHPs produced persistent erectile and urinary tract dysfunction. Periurethral injection of CXCL-12 was feasible and improved both urinary incontinence and erectile dysfunction and suggests that this model can be used to test new approaches for both conditions.

Background: Cell therapy for intrinsic urinary sphincter deficiency (ISD) in women has been moderately effective, and improvements are needed. To improve treatment efficacy, it is important to better understand determinates of cell efficacy in the different patient cohorts. We have reported that in nonhuman primates the chronicity of ISD may affect cell efficacy, but additional factors (age, psychosocial stress, hormone status, body weight) can be associated with many disease/treatment outcomes in women -and these factors are the focus of this study.Methods: Adult female cynomolgus monkeys were divided into groups: (1) younger (n = 10, 5-8 years of age) versus older (n = 10, 13-18 years of age); (2) age-matched/socially subordinate (n = 15) versus socially dominant (n = 15); and (3) age-matched lower body weight (n = 6) versus higher body weight (n = 6). Autologous skeletal muscle precursor cells (skMPCs, 5 million) were injected into the urinary sphincter 6 weeks after a surgically induced ISD procedure. Resting and pudendal nerve-stimulated maximal urethral pressures (MUP) were measured before, and 3 and 6 months post-skMPC treatment and urinary sphincter muscle/collagen content within the sphincter complex was measured by quantitative histology 6 months posttreatment.Results: Efficacy of skMPCs on MUP and sphincter muscle/collagen ratios are affected by age (average 40% reduction in efficacy, p Conclusion: Multiple factors (age, stress-induced dysmenorrhea, and body weight) affect the efficacy of cell therapy to restore structure and function in the urinary sphincter complex in NHPs with ISD. Consideration of, and alternatives for, these patient cohorts should be considered.

We measured the long-term efficacy of autologous muscle precursor cell therapy in premenopausal female nonhuman primates with sustained urinary sphincter deficiency.Urinary sphincter deficiency was created in adult premenopausal female cynomolgus monkeys by selectively cauterizing and then transecting the pudendal innervation to the sphincter complex. The monkeys were then treated (18) or not treated (18) with intra-urinary sphincter injections of 5 million autologous green fluorescent protein labeled skeletal muscle precursor cells. Four untreated, uninjured monkeys served as controls. Maximal urethral pressure measurement and corresponding histological analysis of the structural and cellular components of the sphincter complex were performed up to 12 months after injection.Cell treatment produced sustained (12 months) increases in resting, somatic nerve stimulated and adrenergic nerve stimulated maximal urethral pressure, and a greater percent of sphincter area occupied by muscle as well as a decrease in the sphincter area occupied by collagen compared to the untreated group (each p0.05). These results were within control values (each p0.05). By 3 months after injection green fluorescent protein positive cells were found in the skeletal muscle layer, expressing desmin and connexin-43, and in the smooth muscle layer, expressing α-smooth muscle actin and connexin-43, and they were incorporated into the subendothelial vasculature, expressing Von Willebrand factor. Cell injected sphincter tissue contained a mixture of green fluorescent protein positive cells and predominantly green fluorescent protein negative cells.Injected skeletal muscle progenitor cells incorporated into the injured sphincter complex resulted in long-term structural and functional restoration of the injured sphincter complex in this nonhuman primate model.

The pathophysiology of urinary sphincter deficiency in women remains incompletely understood and current treatment options have limitations. Female nonhuman primates may represent a relevant animal model for studies of pathophysiology and treatment interventions because of their human-like reproductive and age associated stages of life (premenopause, perimenopause and postmenopause), lower urinary tract structure and bipedal posture. We developed and characterized a nonhuman primate model of defined injury to the urethral sphincter complex.We used 22 adult female cynomolgus monkeys in which injury to the sphincter complex was created by cauterizing and then transecting its pudendal innervation. Urodynamic studies were performed before and during pudendal and hypogastric nerve stimulation at baseline, and 3, 6 and 12 months after injury. We also analyzed sphincter structure in vivo by cystourethrography, and ex vivo by quantitative histology and immunohistochemistry at these time points.Injury produced a 47% to 50% decrease in maximal urethral pressure (vs baseline p0.05). It also abolished the increase in maximal urethral pressure in response to pudendal and hypogastric nerve stimulation (vs baseline p0.05), which persisted more than 12 months after injury. Urodynamic changes were consistent with decreased skeletal and smooth muscle content, decreased nerve responses and an associated decrease in somatic and adrenergic innervation in the sphincter complex.These structural and urodynamic changes are consistent with those in patients with stress urinary incontinence. They support the usefulness of nonhuman primates as translatable surrogates for pathophysiological studies of urinary sphincter deficiency and testing novel therapies for that condition.

Background Many factors may influence the efficacy of cell therapy for intrinsic urinary sphincter deficiency (ISD), including the route of administration of the cells and the condition of the sphincter. The goal of this study was to compare local versus intravenous administration of autologous skeletal muscle precursor cells (skMPCs) when administered to nonhuman primates (NHPs) with either acute or chronic ISD. Methods Thirty-two adult female monkeys were divided into eight groups (n = 4/group): (1) control; (2) surgically induced ISD/no treatment; (3) acute ISD (6-week duration)/local vehicle only; (4) acute ISD/local skMPC injection; (5) acute ISD/systemic skMPC; (6) chronic ISD (6-month duration)/local vehicle; (7) chronic ISD/local skMPC; (8) chronic ISD/systemic skMPC. Maximal urethral pressures (MUP) were measured prior to ISD, prior to treatment and at 3 and 6 months following treatment. Quantitative histology was used to measure muscle/collagen content, somatic innervation, and vascularity of the sphincter complexes. Results In NHPs with acute ISD both systemic and local administration of skMPCs increased resting MUP values and sphincter muscle content (p p > 0.05). In NHPs with chronic ISD local skMPC administration had reduced (compared to NHPs with acute ISD) effects on MUP and sphincter muscle values (p p Conclusions Both the chronicity of ISD and the route of cell injection influence the efficacy of cell therapy in monkey models of ISD. This may be related to the relative ability of cells to stimulate vascularization and re-innervation in these different treatment conditions.

Penile repair and reconstruction are needed for a variety of diseases and injuries, including Peyronie’s disease, hypospadias, epispadias, urethral stricture, penis fractures, burns, bites, infections, penetrating injuries, and blunt force trauma [1–4]. Damage to penile tissue often leads to loss of sexual function that can profoundly affect quality of life. When the penile defect or injury is sufficiently large, cannot be managed conservatively, and involves the urethra and rupture of the tunica albuginea and corpora cavernosum, various surgical procedures, such as penile prostheses and autograft implantation, are required. While cosmetic appearance may be improved with these procedures, restoration of spontaneous and natural erectile function is usually not achieved. This is often due to critical defect of the corpora cavernosa, which is responsible for erectile function.

Locally injected skeletal muscle precursor cells (skMPCs) integrate into and restore the muscle layers, innervation, vasculature, and function of the sphincter complex in animal models of intrinsic urinary sphincter deficiency (ISD). The goal of the present study was to test the dose-effect safety profile of skMPC therapy in a dog model of ISD. Sphincter deficiency was created in 20 adult female dogs by surgically removing the skeletal muscle layer of the urinary sphincter complex. skMPCs isolated from the hind leg were expanded in culture and injected 4 weeks later into the sphincter complex at a dose of 25 million cells (n = 5), 50 million cells (n = 5), or 100 million cells (n = 5) per milliliter in a 2-ml volume. Five dogs received no sphincter injection. The measures of maximal sphincter pressure, complete blood count, and blood chemistry were performed monthly until their sacrifice at 9 months. At that point, full necropsy was performed to assess the safety of the skMPC injections. Injection of different doses of cells had no effects on the body weight, blood cell count, or kidney or liver function test results (p > .05 among the skMPC doses). Some incidental pathologic features were found in the lower urinary tract in all groups and were most likely associated with repeat catheterization. The maximal urinary sphincter pressure was higher in the 50 million cells per milliliter treatment group than in the other experimental groups (p < .05). The findings of the present study have confirmed that urinary sphincter injection of skMPCs results in no significant local or systemic pathologic features within the dose range that improves sphincter pressures.

The history of the Yaqui Valley reveals an intricate story of a place constantly facing and adjusting to change over time. From its management for thousands of years by the Yaqui Amerindians to its current state as a highly productive breadbasket, this rich coastal plain has provided food and other essentials for its inhabitants, has been contested ground among many different groups, and, more recently, has become an interesting model of agricultural development for the developing world. This short history attempts to trace those transitions to the present. Many of the issues raised here, especially in the most recent history, are the focus of the chapters to come.

Background: Erythrocyte stimulating agents, iron replacement, and blood transfusions are options in the treatment of chronic anemia. Patients with iron deficiency anemia who cannot tolerate or unable to absorb oral iron may receive intravenous iron. Recent studies have been conducted proving the effectiveness of total-dose low molecular weight iron dextran for the treatment of chronic anemia. Low molecular weight iron dextran (Infed) is FDA approved for to treat iron-deficient anemia and is generally safe and effective. Low molecular weight iron dextran was chosen for this review due to decrease in reported adverse reactions in the literature as compared to high molecular weight iron dextran. Iron dextran may be administered as total dose infusion in one dose, whereas other forms of IV iron require multiple doses for iron replacement. Blood conservancy programs are evaluating ways to reduce blood transfusion requirements due to limitations of available blood supply, transfusion reactions, fluid restrictions and iron overload. We report a retrospective review of the St Joseph/Candler Health System (SJCHS) experience with total dose iron dextran (Infed). Methods: September 2006 to September 2007, 181 adult patients with anemia of chronic disease that were treated with iron dextran (Infed) were identified. Inclusion criteria were patients with anemia of chronic disease, to include hematological and non-hematological malignancies, iron dextran infusion greater than 200mg and anemia defined as hemoglobin level ≤10.5g/dl. A total of 54 patients met the inclusion criteria. There were 27 patients in the study group, which was identified as patients who received total-dose iron dextran (Infed), 27 patients in the control group, which was identified as patients who received a transfusion and no IV iron. Patients that received epoetin were excluded from the review. Age, gender, height, weight, diagnosis, tests of iron status (serum ferritin concentration, transferrin concentration/TIBC, serum iron, and transferrin saturation), CBC, vitamin B12 level, temperature, blood pressure, dose of iron dextran, number of transfusions, and signs or reports of adverse reactions was recorded. All uses of premedication and medications to treat adverse reactions were recorded. Results: In the iron group 85.2%(23/27) did not require blood transfusion. In the transfusion group 70.4%(19/27) required only one transfusion and reached an adequate hemoglobin response. The p-value was 0.19. The average dose of iron dextran(Infed) was 1000mg. The average number of transfusion at treatment failure was 2.25 in the Infed group and 2 in the transfusion alone group. Average hemoglobin prior to iron infusion was 8.8 and prior to initial transfusion was 7.54. Infed patients that were transfused has an average hemoglobin of 8.1 prior to transfusion and 2nd transfusion patients (transfusion alone arm) had a hemoglobin of 8.29 when transfused a second time. No patients in either group had reports of adverse reactions. However, in the screening phase of the study 9 out of 181 patients (4.9%) had a documented adverse reaction to the iron test dose. All of these patients may have received Dexferrum, not Infed, and were excluded from the review. In the iron group 44.4% of patients had a hemoglobin(HgB) response greater than or equal to 10gm/dL. In the transfusion group 48.1% of patients had a hemoglobin response of greater than or equal to 10gm/dL. The p-value was 0.78. Conclusion: Total-dose iron dextran was equally effective at reducing the incidence of transfusion compared to the transfusion control group. Both groups were equally effective at achieving a hemoglobin of greater that or equal to 10 gm/dL. This review should result in increased use of total-dose iron dextran in patients with chronic anemia without iron overload, decreased the number of transfusions by using total-dose iron dextran when appropriate, and increased awareness of intravenous iron replacement therapy.